Tasmar

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Tasmar

Before prescribing TASMAR, the physician should be
thoroughly familiar with the details of this prescribing information.

TASMAR SHOULD NOT BE USED BY PATIENTS UNTIL THERE HAS
BEEN A COMPLETE DISCUSSION OF THE RISKS AND THE PATIENT HAS PROVIDED WRITTEN
ACKNOWLEDGEMENT THAT THE RISKS HAVE BEEN EXPLAINED (SEE PATIENT
ACKNOWLEDGEMENT OF RISKS SECTION).

Because of the risk of potentially fatal, acute
fulminant liver failure, TASMAR (tolcapone) should ordinarily be used in
patients with Parkinson's disease on l-dopa/carbidopa who are experiencing
symptom fluctuations and are not responding satisfactorily to or are not
appropriate candidates for other adjunctive therapies (see INDICATIONS and
DOSAGE AND ADMINISTRATION sections).

Because of the risk of liver injury and because
TASMAR, when it is effective, provides an observable symptomatic benefit, the
patient who fails to show substantial clinical benefit within 3 weeks of
initiation of treatment, should be withdrawn from TASMAR.

TASMAR therapy should not be initiated if the patient
exhibits clinical evidence of liver disease or two SGPT/ALT or SGOT/AST values
greater than the upper limit of normal. Patients with severe dyskinesia or
dystonia should be treated with caution (see PRECAUTIONS: Rhabdomyolysis).

PATIENTS WHO DEVELOP EVIDENCE OF HEPATOCELLULAR INJURY
WHILE ON TASMAR AND ARE WITHDRAWN FROM THE DRUG FOR ANY REASON MAY BE AT
INCREASED RISK FOR LIVER INJURY IF TASMAR IS REINTRODUCED. ACCORDINGLY, SUCH
PATIENTS SHOULD NOT ORDINARILY BE CONSIDERED FOR RETREATMENT.

Cases of severe hepatocellular injury, including
fulminant liver failure resulting in death, have been reported in postmarketing
use. As of May 2005, 3 cases of fatal fulminant hepatic failure have been
reported from more than 40,000 patient years of worldwide use. This incidence
may be 10- to 100-fold higher than the background incidence in the general
population. Underreporting of cases may lead to significant underestimation of
the increased risk associated with the use of TASMAR. All 3 cases were reported
within the first six months of initiation of treatment with TASMAR. Analysis of
the laboratory monitoring data in over 3,400 TASMAR-treated patients
participating in clinical trials indicated that increases in SGPT/ALT or
SGOT/AST, when present, generally occurred within the first 6 months of
treatment with TASMAR.

A prescriber who elects to use TASMAR in face of the
increased risk of liver injury is strongly advised to monitor patients for
evidence of emergent liver injury. Patients should be advised of the need for
self-monitoring for both the classical signs of liver disease (e.g., clay
colored stools, jaundice) and the nonspecific ones (eg, fatigue, loss of
appetite, lethargy).

Although a program of periodic laboratory monitoring
for evidence of hepatocellular injury is recommended, it is not clear that
periodic monitoring of liver enzymes will prevent the occurrence of fulminant
liver failure. However, it is generally believed that early detection of
drug-induced hepatic injury along with immediate withdrawal of the suspect drug
enhances the likelihood for recovery. Accordingly, the following liver
monitoring program is recommended.

Before starting treatment with TASMAR, the physician
should conduct appropriate tests to exclude the presence of liver disease. In
patients determined to be appropriate candidates for treatment with TASMAR,
serum glutamic-pyruvic transaminase (SGPT/ALT) and serum glutamic-oxaloacetic
transaminase (SGOT/AST) levels should be determined at baseline and
periodically (i.e. every 2 to 4 weeks) for the first 6 months of therapy. After
the first six months, periodic monitoring is recommended at intervals deemed
clinically relevant. Although more frequent monitoring increases the chances of
early detection, the precise schedule for monitoring is a matter of clinical
judgment. If the dose is increased to 200 mg tid (see DOSAGE AND ADMINISTRATION section), liver enzyme monitoring should take place before increasing the dose
and then be conducted every 2 to 4 weeks for the following 6 months of therapy.
After six months, periodic monitoring is recommended at intervals deemed
clinically relevant.

TASMAR should be discontinued if SGPT/ALT or SGOT/AST
levels exceed 2 times the upper limit of normal or if clinical signs and
symptoms suggest the onset of hepatic dysfunction (persistent nausea, fatigue,
lethargy, anorexia, jaundice, dark urine, pruritus, and right upper quadrant
tenderness).

DRUG DESCRIPTION

TASMAR® is available as tablets containing 100
mg tolcapone.

Tolcapone, an inhibitor of catechol-O-methyltransferase
(COMT), is used in the treatment of Parkinson's disease as an adjunct to
levodopa/carbidopa therapy. It is a yellow, odorless, non-hygroscopic,
crystalline compound with a relative molecular mass of 273.25. The chemical
name of tolcapone is 3,4-dihydroxy-4'-methyl-5nitrobenzophenone. Its empirical
formula is C14H11NO5 and its structural
formula is:

What are the precautions when taking tolcapone (Tasmar)?

See also Warning section.

Before taking tolcapone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.